SUMMARY ABSTRACT There have been many recent developments in invasive and non-invasive techniques for modulating brain operations. However, these techniques typically cannot be efficiently used beyond ?proof of concept? experiments since the cellular-network origins of the most basic functions in the brain are not known. Part of the reason for this is that while cognitive neuroscientists have learned a lot about the principles that govern brain operations, and computational modelers have made leaps and bounds in creating models of nearly every brain circuit, these two fields remain only sparsely connected. Our proposed project will bridge the gap between cognitive neuroscience, electrophysiology, and computational modeling by measuring neuronal activity on multiple spatial scales in behavioral experiments, and connecting these data to detailed computational models of the auditory thalamocortical system. This process will provide specific predictions for the neuromodulation of auditory system function and form a solid base for novel therapeutic approaches. Our project focuses on defining the cellular-network underpinnings of three distinct mechanisms of auditory perceptual processes, which are utilized for speech processing. The first is the flexibility of neuronal oscillations in the delta-theta bands that endows them with the capability to dynamically adapt their cycles to the quasi-rhythmic structure of naturalistic auditory stimulus sequences, including species specific vocalizations and speech. The second mechanism that supports efficient auditory processing is oscillatory phase reset, which enables the precise tracking of stimulus sequences by neuronal oscillations supporting, amongst other things the figure-ground segregation of attended auditory streams. The third fundamental mechanism for processing continuous auditory stimulus streams is parsing, which enables the brain to segment and group acoustic elements so that they form units that are interpretable by the brain. These three mechanisms form the basis of the complex computations needed to make sense of the auditory environment. We will perform concurrent thalamus-cortex electrophysiological recordings in macaques to determine the spatiotemporal organization of neuronal activity patterns supporting the above described fundamental auditory processing mechanisms. The data collected during behavioral tasks will inform our detailed thalamocortical computational model, which will in turn provide precise predictions on efficient neuromodulation approaches to induce, or temporarily inhibit the neuronal activity patterns underlying distinct auditory processes like stream segregation or parsing. Besides advanced time-resolved single unit and neuronal ensemble activity analyses, we will be able to verify the effectiveness of neuromodulation based on behavioral biases. The model based, targeted neuromodulation techniques developed by our proposed projects will pave the way for novel therapeutic approaches in the treatment of neuropsychiatric and developmental disorders that are hallmarked by deficits in the dynamical properties of neuronal oscillatory systems.